DESCRIPTION(Adapted from applicant's abstract): One of the most disabling sequelae to brain injury (BI), stroke, cerebral palsy (CP), spinal cord injury (SCI), spinal degenerative diseases such as multiple sclerosis (MS) and familial spastic paraparesis is the development of spastic hypertonia. The systemic delivery of gamma-amino-butyric acid (GABA) agonists has been successfully utilized for decades to reduce the spastic hypertonia. The GABA-B agonist baclofen has been delivered intrathecally into the cerebrospinal fluid surrounding the spinal cord. Side effects associated with systemic delivery are minimized with intrathecal administration. Gamma-amino-butyramide hydrochloride (GABAmide), which is an active metabolite of Progabide, is both a GABA-A as well as a GABA-B receptor agonist. We propose to conduct the final stage of pre-clinical testing of a drug, GABAmide. The effective intrathecal dose would be less than 1/100 to l /1000 of the necessary systemic delivery. Because of its broader receptor effects than baclofen, it is likely that intrathecally delivered GABAmide would be more than baclofen. Our preliminary studies in rats confirm that intrathecal GABAmide reduces spasticity at low doses. Proposed is a double-blind randomized crossover trial of intrathecally delivered GABAmide versus baclofen and normal saline in a rat model. This is to develop further knowledge on appropriate dosing and efficacy, before starting phase I human trials. PROPOSED COMMERCIAL APPLICATION: This would allow the development of a competitor to intrathecally delivered baclofen, which currently can run from $825 to over $1000 per refill kit. (pumps are refilled every one to three months). In US today, there are thousands of patients with implanted pumps that deliver intrathecal baclofen to treat disabling spastic hypertonia from SCI, MS, TBI, stroke, or CP. Development of a more effective alternative to intrathecally-delivered baclofen would allow for a significant profit and still decrease the cost of this effective treatment system.